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阳离子固体脂质纳米粒在针对内脏利什曼病的 DNA 疫苗接种中与电穿孔一样有效,在小鼠中。

Cationic solid-lipid nanoparticles are as efficient as electroporation in DNA vaccination against visceral leishmaniasis in mice.

机构信息

Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Parasite Immunol. 2013 Dec;35(12):397-408. doi: 10.1111/pim.12042.

Abstract

The use of an appropriate delivery system has recently emerged as a promising approach for the development of effective vaccination against visceral leishmaniasis (VL). Here, we compare two vaccine delivery systems, namely electroporation and cationic solid-lipid nanoparticle (cSLN) formulation, to administer a DNA vaccine harbouring the L. donovani A2 antigen along with L. infantum cysteine proteinases [CPA and CPB without its unusual C-terminal extension (CPB(-CTE) )] and evaluate their potential against L. infantum challenge. Prime-boost administration of the pcDNA-A2-CPA-CPB(-CTE) delivered by either electroporation or cSLN formulation protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-γ and lower levels of IL-10 production, leading to a strong Th1 immune response. At all time points, the ratio of IFN-γ: IL-10 induced upon restimulation with rA2-rCPA-rCPB and F/T antigens was significantly higher in vaccinated animals. Moreover, Th2-efficient protection was elicited through a high humoral immune response. Nitric oxide production, parasite burden and histopathological analysis were also in concordance with other findings. Overall, these data indicate that similar to the electroporation delivery system, cSLNs as a nanoscale vehicle of Leishmania antigens could improve immune response, hence indicating the promise of these strategies against visceral leishmaniasis.

摘要

最近,人们发现使用适当的传递系统是开发针对内脏利什曼病(VL)的有效疫苗的一种很有前途的方法。在这里,我们比较了两种疫苗传递系统,即电穿孔和阳离子固体脂质纳米颗粒(cSLN)制剂,以给予携带 L. donovani A2 抗原的 DNA 疫苗,以及 L. infantum 半胱氨酸蛋白酶 [CPA 和 CPB 而没有其不寻常的 C 末端延伸(CPB(-CTE))],并评估它们针对 L. infantum 挑战的潜力。通过电穿孔或 cSLN 制剂传递的 pcDNA-A2-CPA-CPB(-CTE)的初免-加强给药可保护 BALB/c 小鼠免受 L. infantum 挑战的侵害,并且这种保护免疫力与高水平的 IFN-γ和较低水平的 IL-10 产生有关,导致强烈的 Th1 免疫反应。在所有时间点,在用 rA2-rCPA-rCPB 和 F/T 抗原再刺激时诱导的 IFN-γ:IL-10 的比值在接种动物中显着更高。此外,通过高体液免疫反应引发了 Th2 有效的保护。一氧化氮产生,寄生虫负担和组织病理学分析也与其他发现一致。总体而言,这些数据表明,类似于电穿孔传递系统,作为利什曼抗原的纳米级载体的 cSLN 可以改善免疫反应,从而表明这些策略在治疗内脏利什曼病方面具有潜力。

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